Allergic diseases have reached epidemic proportions worldwide and are generally accepted to be increasing. Allergy symptoms are treated efficiently with cheap small molecule drugs in most patients, but none are curative. However, there is a clear unmet medical need for patients suffering persistent asthma. Current standard treatment for inflammatory diseases include immunosuppressing or immunomodulating medications such as (but not limited to) corticosteroids, non-steroidal anti inflammatory drugs, TNF-alpha antagonists, cytokine(receptor) agonists or antagonists. Current standard treatment for allergic asthma include inhaled or systemically administered corticosteroids in combination with inhaled (long or short acting) Beta-2 agonists, possibly combined with medications such as (but not limited to) Leukotriene receptor antagonists, theophylline, cromolyn, nedocromyl.
The introduction of monoclonal antibodies and soluble cytokine receptors is revolutionizing approaches to the treatment of asthma and allergy. The successful introduction of omalizumab (anti IgE) for severe allergic asthma has stimulated great interest in this approach, but even with this humanised monoclonal antibody, cost effectiveness analyses are restricting its use even though it has passed scrutiny by such agents as the National Institute of Health & Clinical Excellence in the UK. Also, substantial portions of the potential patient population in asthma have IgE levels higher than can successfully be neutralized with the current molecule. A more potent inhibitor is required for these, and attempts have been made to produce such a molecule.
Understanding the underlying mechanisms of allergic disease has stimulated the further development of a series of biologics targeted towards critical cells and molecules. Because of the sentinel roles of Th2 cells and their products, Th2 cytokines, in orchestrating allergic inflammation, they and their receptors are key therapeutic targets. One of these is the TNF family member “OX40L” (Review: Michael J. Gough et al., Therapeutic Targets of the TNF superfamily, edited by Iqbal S. Grewal, 2007). OX40L and antibodies against OX40L which are able to disrupt binding of OX40L to its receptor OX40 (and thus inhibit the relevant signaling cascade) are mentioned in e.g. WO95/12673, WO95/21915, WO99/15200, WO2006/029879, WO2005/094879 and WO2007/133290.